Cooperative interactions facilitate stimulation of Rad51 by the Swi5-Sfr1 auxiliary factor complex

eLife

Yasuto Murayama¹  Masayoshi Sakakura²  Hideo Takahashi²  Misato Kurihara²  Kentaro Ito³  Bilge Argunhan³  Takahisa Maki³  Negar Afshar⁴  Shuji Kanamaru⁴  Hiroshi Iwasaki⁴  Hideo Tsubouchi⁴  Masayuki Takahashi⁵ 

[1] Center for Frontier Research, National Institute of Genetics, Shizuoka, Japan;Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan;Institute of Innovative Research, Tokyo Institute of Technology, Tokyo, Japan;Institute of Innovative Research, Tokyo Institute of Technology, Tokyo, Japan;School of Life Science and Technology, Tokyo Institute of Technology, Tokyo, Japan;School of Life Science and Technology, Tokyo Institute of Technology, Tokyo, Japan;

关键词: DNA repair;    homologous recombination;    Rad51;    Swi5-Sfr1;    Rad55-Rad57;    disordered;    S. pombe;   

DOI  :  10.7554/eLife.52566

来源: publisher

【 摘 要 】

Although Rad51 is the key protein in homologous recombination (HR), a major DNA double-strand break repair pathway, several auxiliary factors interact with Rad51 to promote productive HR. We present an interdisciplinary characterization of the interaction between Rad51 and Swi5-Sfr1, a conserved auxiliary factor. Two distinct sites within the intrinsically disordered N-terminus of Sfr1 (Sfr1N) were found to cooperatively bind Rad51. Deletion of this domain impaired Rad51 stimulation in vitro and rendered cells sensitive to DNA damage. By contrast, amino acid-substitution mutants, which had comparable biochemical defects, could promote DNA repair, suggesting that Sfr1N has another role in addition to Rad51 binding. Unexpectedly, the DNA repair observed in these mutants was dependent on Rad55-Rad57, another auxiliary factor complex hitherto thought to function independently of Swi5-Sfr1. When combined with the finding that they form a higher-order complex, our results imply that Swi5-Sfr1 and Rad55-Rad57 can collaboratively stimulate Rad51 in Schizosaccharomyces pombe.

【 授权许可】

CC BY